Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism

Stem Cell Research & Therapy

Research

Wei Chen¹  Xinyue Li²  Le Guo²  Yi Liu²  Jingan Chen²  Hui Wang²  Haowei Liang²  Li Zhou³  Letian Shan⁴ 

[1]Cancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, 234 Gucui Road, 310012, Hangzhou, Zhejiang, China

[2]School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China

[3]The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China

[4]The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China

[5]Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China

关键词: Human umbilical cord-derived mesenchymal stem cells;    Diabetic nephropathy;    Podocytes;    Paracrine effect;    AMPK/mTOR signaling;   

DOI  :  10.1186/s13287-023-03354-z

 received in 2022-07-20, accepted in 2023-04-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDiabetic nephropathy (DN) is one of the most severe complications of diabetes mellitus, which is characterized by early occurrence of albuminuria and end-stage glomerulosclerosis. Senescence and autophagy of podocytes play an important role in DN development. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have potential in the treatment of diabetes and its complications. However, the role of hucMSCs in the treatment of DN and the underlying mechanism remain unclear.MethodsIn vivo, a streptozotocin-induced diabetic male Sprague Dawley rat model was established to determine the renoprotective effect of hucMSCs on DN by biochemical analysis, histopathology, and immunohistochemical staining of renal tissues. And the distribution of hucMSCs in various organs in rats within 168 h was analyzed. In vitro, CCK8 assay, wound healing assay, and β-galactosidase staining were conducted to detect the beneficial effects of hucMSCs on high glucose-induced rat podocytes. Real-time PCR and western blot assays were applied to explore the mechanism of action of hucMSCs.ResultsThe in vivo data revealed that hucMSCs were distributed into kidneys and significantly protected kidneys from diabetic damage. The in vitro data indicated that hucMSCs improved cell viability, wound healing, senescence of the high glucose-damaged rat podocytes through a paracrine action mode. Besides, the altered expressions of senescence-associated genes (p16, p53, and p21) and autophagy-associated genes (Beclin-1, p62, and LC3) were improved by hucMSCs. Mechanistically, hucMSCs protected high glucose-induced injury in rat podocytes by activating autophagy and attenuating senescence through the AMPK/mTOR pathway.ConclusionsIn conclusion, hucMSCs might be a promising therapeutic strategy for the clinical treatment of DN-induced renal damages.

【 授权许可】

CC BY   
© The Author(s) 2023

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